JAC Advance Access published online on February 4, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh078
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Wyeth Research, 401 N.
Middletown Rd., Pearl River, NY 10965;
* Corresponding author. E-mail: weissw{at}wyeth.com.
Received 20 August 2003
; revised 11 November 2003
; accepted 17 November 2003
Objective: The role that the surface
proteins anchored by the srtA and srtB gene
products play in the ability of Staphylococcus aureus bacteria
to establish infection was investigated in several animal models. Methods: Wild-type and corresponding mutants
with deletions of the srtA and/or srtB genes
were used in murine acute lethal infection, septic arthritis, kidney
infection and rat endocarditis models. Results: The LD50 of the wild-type
and srtB- knockout were comparable and
approximately two- to four-fold lower than the required inoculum
of the srtA- and srtA-B- strains.
This difference was exhibited as a two-fold greater mortality at
the highest inoculum. The wild-type strain established arthritic
inflammation in over 90% of the animals with a maximum
arthritic index of 6.5 by days 17-21. The srtB- knockout
was able to cause inflammation in 70-80% of the
mice, but with a lower index of 3.0. Both the srtA- and srtA-B- strains appeared to be
less virulent in this model with arthritic indices of around 0.5
and only 20% of the animals with inflammation. Strains
with the srtA mutation achieved statistically significant
lower titres than wild-type in kidneys of mice after intravenous
infection. Mean bacterial counts in cardiac vegetations were significantly higher
for the wild-type and srtB- strain compared
with the srtA- and srtA-B- strains. Conclusion: Results from this study substantiate
the role of the srtA gene product in the establishment
of infections and further studies are warranted to define and exploit
this as a target for antimicrobial chemotherapy.
Keywords: sortase, virulence, arthritis, endocarditis
Effect of srtA and srtB gene
expression on the virulence of Staphylococcus aureus in
animal models of infection
2 Committee on Microbiology,
University of Chicago, Chicago, IL, USA
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